Transgenic human embryonic stem cells overexpressing FGF2 stimulate neuroprotection following spinal cord ventral root avulsion.


:Ventral root avulsion (VRA) triggers a strong glial reaction which contributes to neuronal loss, as well as to synaptic detachment. To overcome the degenerative effects of VRA, treatments with neurotrophic factors and stem cells have been proposed. Thus, we investigated neuroprotection elicited by human embryonic stem cells (hESC), modified to overexpress a human fibroblast growth factor 2 (FGF-2), on motoneurons subjected to VRA. Lewis rats were submitted to VRA (L4-L6) and hESC/FGF-2 were applied to the injury site using a fibrin scaffold. The spinal cords were processed to evaluate neuronal survival, synaptic stability, and glial reactivity two weeks post lesion. Then, qRT-PCR was used to assess gene expression of β2-microglobulin (β2m), TNFα, IL1β, IL6 and IL10 in the spinal cord in vivo and FGF2 mRNA levels in hESC in vitro. The results indicate that hESC overexpressing FGF2 significantly rescued avulsed motoneurons, preserving synaptic covering and reducing astroglial reactivity. The cells were also shown to express BDNF and GDNF at the site of injury. Additionally, engraftment of hESC led to a significant reduction in mRNA levels of TNFα at the spinal cord ventral horn, indicating their immunomodulatory properties. Overall, the present data suggest that hESC overexpressing FGF2 are neuroprotective and can shift gene expression towards an anti-inflammatory environment.


Exp Neurol


Experimental neurology


Araújo MR,Kyrylenko S,Spejo AB,Castro MV,Ferreira Junior RS,Barraviera B,Oliveira ALR




Has Abstract


2017-08-01 00:00:00












  • Ethanol withdrawal induces increased firing in inferior colliculus neurons associated with audiogenic seizure susceptibility.

    abstract::Ethanol withdrawal (ETX) in ethanol-dependent rats results in susceptibility to seizures, including generalized tonic-clonic audiogenic seizures (AGS). The inferior colliculus (IC) is strongly implicated in AGS initiation during ETX, but IC neuronal mechanisms subserving AGS are unclear. The present study examined IC ...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Faingold CL,Riaz A

    更新日期:1995-03-01 00:00:00

  • c-Fos expression mediated by N-methyl-D-aspartate receptors following anodal polarization in the rat brain.

    abstract::c-Fos protein-like immunoreactivity (IR) was investigated in the rat brain following an application of weak anodal direct current to the surface of the unilateral sensorimotor cortex in an attempt to elucidate the cellular and molecular bases of central plasticity. Anodal polarization resulted in a massive increase in...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Islam N,Moriwaki A,Hattori Y,Hayashi Y,Lu YF,Hori Y

    更新日期:1995-05-01 00:00:00

  • Amyloid beta peptides and glutamatergic synaptic dysregulation.

    abstract::Alzheimer's disease (AD) is a major neurodegenerative disorder in which overproduction and accumulation of amyloid beta (Abeta) peptides result in synaptic dysfunction. Recent reports strongly suggest that in the initial stages of AD glutamate receptors are dysregulated by Abeta accumulation resulting in disruption of...

    journal_title:Experimental neurology

    pub_type: 杂志文章,评审


    authors: Parameshwaran K,Dhanasekaran M,Suppiramaniam V

    更新日期:2008-03-01 00:00:00

  • Intranasal cotinine improves memory, and reduces depressive-like behavior, and GFAP+ cells loss induced by restraint stress in mice.

    abstract::Posttraumatic stress disorder (PTSD), chronic psychological stress, and major depressive disorder have been found to be associated with a significant decrease in glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus of rodents. Cotinine is an alkaloid that prevents memory impairment, depressive-li...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Perez-Urrutia N,Mendoza C,Alvarez-Ricartes N,Oliveros-Matus P,Echeverria F,Grizzell JA,Barreto GE,Iarkov A,Echeverria V

    更新日期:2017-09-01 00:00:00

  • Peripherally administered insulin-like growth factor-I preserves hindlimb reflex and spinal cord noradrenergic circuitry following a central nervous system lesion in rats.

    abstract::The blood-central nervous system-barrier (B-CNS-B) is widely considered a significant impediment to the use of protein neurotrophic factors for the treatment of brain diseases and disorders. In this study, we tested the hypothesis that systemic administration of insulin-like growth factor I (IGF-I) can ameliorate func...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Pulford BE,Whalen LR,Ishii DN

    更新日期:1999-09-01 00:00:00

  • In vivo microdialysis studies on somatodendritic dopamine release in the rat substantia nigra: effects of unilateral 6-OHDA lesions and GDNF.

    abstract::Dopamine (DA) release and metabolism within the substantia nigra (SN) were studied in normal rats, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions, and 6-OHDA-lesioned rats treated with glial cells line-derived neurotrophic factor (GDNF). Animals with > 99% DA depletions, as determined by apomorphine-induced c...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Hoffman AF,van Horne CG,Eken S,Hoffer BJ,Gerhardt GA

    更新日期:1997-09-01 00:00:00

  • Microglial and astroglial reactions to ischemic and kainic acid-induced lesions of the adult rat hippocampus.

    abstract::The aim of this study was to characterize the microglial and astroglial reactions to degeneration of (a) hippocampal CA1 pyramidal cells and dentate hilar neurons induced by cerebral ischemia and (b) CA3 pyramidal cells and dentate hilar neurons induced by intraventricular injections of kainic acid (KA). The microglia...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Jørgensen MB,Finsen BR,Jensen MB,Castellano B,Diemer NH,Zimmer J

    更新日期:1993-03-01 00:00:00

  • The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury.

    abstract::Chondroitin sulfate proteoglycans (CSPGs) are extracellular matrix (ECM) molecules that are widely expressed throughout the developing and adult CNS. In vitro studies demonstrate their potential to restrict neurite outgrowth, and it is believed that CSPGs also inhibit axonal regeneration after CNS injury in vivo. Prev...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Jones LL,Margolis RU,Tuszynski MH

    更新日期:2003-08-01 00:00:00

  • Bilateral tactile hypersensitivity and neuroimmune responses after spared nerve injury in mice lacking vasoactive intestinal peptide.

    abstract::Vasoactive intestinal peptide (VIP) is one of the neuropeptides showing the strongest up-regulation in the nociceptive pathway after peripheral nerve injury and has been proposed to support neuropathic pain. Nevertheless, the story may be more complicated considering the known suppressive effects of the peptide on the...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Gallo A,Leerink M,Michot B,Ahmed E,Forget P,Mouraux A,Hermans E,Deumens R

    更新日期:2017-07-01 00:00:00

  • CD8+-dependent CNS demyelination following ocular infection of mice with a recombinant HSV-1 expressing murine IL-2.

    abstract::Demyelinating diseases comprise a spectrum of immunopathologic syndromes in which myelin, the fatty covering of nerve cell fibers in the brain and spinal cord, is destroyed. In this study, we have shown for the first time that ocular infection of BALB/c mice with a recombinant herpes simplex virus type 1 (HSV-1) expre...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Osorio Y,La Point SF,Nusinowitz S,Hofman FM,Ghiasi H

    更新日期:2005-05-01 00:00:00

  • Phosphatidylinositol-3-kinase-Akt kinase and p42/p44 mitogen-activated protein kinases mediate neurotrophic and excitoprotective actions of a secreted form of amyloid precursor protein.

    abstract::The alpha-secretase-derived form of the amyloid precursor protein (sAPPalpha), which is released from neurons in an activity-dependent manner, has been shown to promote long-term survival of hippocampal and cortical neurons in culture and can protect those neurons against excitotoxic and ischemic injury in culture and...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Cheng G,Yu Z,Zhou D,Mattson MP

    更新日期:2002-06-01 00:00:00

  • Huntington's disease intranuclear inclusions contain truncated, ubiquitinated huntingtin protein.

    abstract::Intranuclear inclusion bodies are a shared pathological feature of Huntington's disease (HD) and its transgenic mouse model. Using a panel of antibodies spanning the entire huntingtin molecule, we have investigated the pattern of immunoreactivity within the intranuclear inclusions in the frontal cortex and striatum of...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Sieradzan KA,Mechan AO,Jones L,Wanker EE,Nukina N,Mann DM

    更新日期:1999-03-01 00:00:00

  • Glutamate induces rapid loss of axonal neurofilament proteins from cortical neurons in vitro.

    abstract::One of the primary hallmarks of glutamate excitotoxicity is degradation of the neuronal cytoskeleton. Using a tissue culture approach, we have investigated the relationship between excitotoxicity and cytoskeletal degradation within axons, with particular reference to the axon specific neurofilament proteins. Neurofila...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Chung RS,McCormack GH,King AE,West AK,Vickers JC

    更新日期:2005-06-01 00:00:00

  • Beta-adrenergic receptor binding in brain of alcoholics.

    abstract::The binding of agonists and antagonists to beta-adrenergic receptors in brain tissue obtained postmortem in nonalcoholic controls and matched intoxicated and sober alcoholics was measured to assess the state of the receptors and their coupling to adenylate cyclase. Binding of antagonist, iodocyanopindolol, to cerebral...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Valverius P,Borg S,Valverius MR,Hoffman PL,Tabakoff B

    更新日期:1989-09-01 00:00:00

  • Differential expression of tenascin-C, tenascin-R, tenascin/J1, and tenascin-X in spinal cord scar tissue and in the olfactory system.

    abstract::The members of the tenascin family are involved in a number of developmental processes, mainly by their ability to regulate cell adhesion. We have here studied the distribution of mRNAs for tenascin-X, -C, and -R and the closely related molecule tenascin/J1 in the olfactory system and spinal cord. The olfactory bulb a...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Deckner M,Lindholm T,Cullheim S,Risling M

    更新日期:2000-12-01 00:00:00

  • Lateralized wall-facing versus turning as measures of behavioral asymmetries and recovery of function after injection of 6-hydroxydopamine into the substantia nigra.

    abstract::The tendency of a rat to approach the wall of an open-field and to travel along the perimeter of the field (termed as "peritaxis" or "wall-facing") is affected by unilateral removal of the vibrissae. Peritaxis is lateralized by hemivibrissotomy. The finding that the dopamine agonist apomorphine reversed the direction ...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Steiner H,Bonatz AE,Huston JP,Schwarting R

    更新日期:1988-03-01 00:00:00

  • New insights into mitochondrial structure during cell death.

    abstract::Mitochondria play a pivotal role in the cascade of events associated with cell death pathways that are involved with several forms of neurodegeneration. Recent findings show that in the Bax/Bak-dependent pathway of apoptosis, the release of cytochrome c from mitochondria is a consequence of two carefully coordinated e...

    journal_title:Experimental neurology

    pub_type: 杂志文章,评审


    authors: Perkins G,Bossy-Wetzel E,Ellisman MH

    更新日期:2009-08-01 00:00:00

  • The "campus syndrome" in pigs: neurological, neurophysiological, and neuropharmacological characterization of a new genetic animal model of high-frequency tremor.

    abstract::Inherited neurological diseases in animals are of interest to a wide range of scientific disciplines, particularly because such animals may be suited as genetic animal models for respective human disorders. Because the pig has a number of anatomic and physiologic features similar to those of human beings, this species...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Richter A,Wissel J,Harlizius B,Simon D,Schelosky L,Scholz U,Poewe W,Löscher W

    更新日期:1995-08-01 00:00:00

  • Neurotrophic properties of olfactory ensheathing glia.

    abstract::Olfactory ensheathing cells (OEC) constitute a specialized population of glia that accompany primary olfactory axons and have been reported to facilitate axonal regeneration after spinal cord injury in vivo. In the present report we describe OEC neurotrophic factor expression and neurotrophic properties of OECs in vit...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Lipson AC,Widenfalk J,Lindqvist E,Ebendal T,Olson L

    更新日期:2003-04-01 00:00:00

  • Impaired axonal transport and altered axolemmal permeability occur in distinct populations of damaged axons following traumatic brain injury.

    abstract::Traumatic axonal injury (TAI) evolves within minutes to hours following traumatic brain injury (TBI). Previous studies have identified axolemmal disruption and impaired axonal transport (AxT) as key mechanisms in the evolution of TAI. While initially hypothesized that axolemmal disruption culminates in impaired AxT, p...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Stone JR,Okonkwo DO,Dialo AO,Rubin DG,Mutlu LK,Povlishock JT,Helm GA

    更新日期:2004-11-01 00:00:00

  • Modification of vestibular-induced pause neuron firing during anesthesia and light sleep.

    abstract::Anatomic and electrophysiologic evidence suggests there is a vestibular input to eye movement-related pause neurons in the midline of the pontine reticular formation of the cat. The present investigation sought to explore the functional significance of this vestibular drive by examining pause neuron response to horizo...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Ito J,Markham CH,Curthoys IS

    更新日期:1987-03-01 00:00:00

  • Dynamics of axonal mRNA transport and implications for peripheral nerve regeneration.

    abstract::Locally generating new proteins in subcellular regions provide means to spatially and temporally modify protein content in polarized cells. Recent years have seen resurgence of the concept that axonal processes of neurons can locally synthesize proteins. Experiments from a number of groups have now shown that axonal p...

    journal_title:Experimental neurology

    pub_type: 杂志文章,评审


    authors: Yoo S,van Niekerk EA,Merianda TT,Twiss JL

    更新日期:2010-05-01 00:00:00

  • Additive effects of caspase inhibitor and lazaroid on the survival of transplanted rat and human embryonic dopamine neurons.

    abstract::Major practical constraints on neural grafting in Parkinson's disease are the shortage of human donor tissue and the great loss of dopamine neurons during the grafting procedure. The vast majority of implanted embryonic dopamine neurons are believed to die within a few days of transplantation surgery, at least in part...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Hansson O,Castilho RF,Kaminski Schierle GS,Karlsson J,Nicotera P,Leist M,Brundin P

    更新日期:2000-07-01 00:00:00

  • Treatment with anti-interferon-gamma monoclonal antibodies modifies experimental autoimmune encephalomyelitis in interferon-gamma receptor knockout mice.

    abstract::The role of interferon-gamma (IFN-gamma) in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) is still controversial. We have studied the function of IFN-gamma and its receptor in the EAE model using two different IFN-gamma receptor knockout (IFN-gamma R(-/-)) mouse types: C57B...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Espejo C,Penkowa M,Sáez-Torres I,Xaus J,Celada A,Montalban X,Martínez-Cáceres EM

    更新日期:2001-12-01 00:00:00

  • Macrophage migration inhibitory factor (MIF) is essential for inflammatory and neuropathic pain and enhances pain in response to stress.

    abstract::Stress and glucocorticoids exacerbate pain via undefined mechanisms. Macrophage migration inhibitory factor (MIF) is a constitutively expressed protein that is secreted to maintain immune function when glucocorticoids are elevated by trauma or stress. Here we show that MIF is essential for the development of neuropath...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Alexander JK,Cox GM,Tian JB,Zha AM,Wei P,Kigerl KA,Reddy MK,Dagia NM,Sielecki T,Zhu MX,Satoskar AR,McTigue DM,Whitacre CC,Popovich PG

    更新日期:2012-08-01 00:00:00

  • Transient up-regulation of retinal EphA3 and EphA5, but not ephrin-A2, coincides with re-establishment of a topographic map during optic nerve regeneration in goldfish.

    abstract::Eph tyrosine kinase receptors and their ligands, the ephrins, play a key role in the establishment of retinotectal topography during development. Tectal up-regulation of ephrin-A2 in goldfish, coincident with the reestablishment of a retinotectal map, suggests a similar role during optic nerve regeneration. Here we re...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: King CE,Wallace A,Rodger J,Bartlett C,Beazley LD,Dunlop SA

    更新日期:2003-10-01 00:00:00

  • P38 MAP kinase is activated at early stages in Alzheimer's disease brain.

    abstract::The regional, cellular, and subcellular localization of phosphorylated p38 MAPK (pp38) was examined by immunocytochemistry, immuofluorescent multiple labeling, and immunoblotting of extracts as well as immunoprecipitates of human postmortem tissue from control and Alzheimer's disease (AD) cases at different Braak stag...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Sun A,Liu M,Nguyen XV,Bing G

    更新日期:2003-10-01 00:00:00

  • Wild-type and mutant huntingtins function in vesicle trafficking in the secretory and endocytic pathways.

    abstract::Huntingtin is a cytoplasmic protein that is found in neurons and somatic cells. In patients with Huntington's disease (HD), the NH2-terminal region of huntingtin has an expanded polyglutamine tract. An abnormal protein interaction by mutant huntingtin has been proposed as a mechanism for HD pathogenesis. Huntingtin as...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Velier J,Kim M,Schwarz C,Kim TW,Sapp E,Chase K,Aronin N,DiFiglia M

    更新日期:1998-07-01 00:00:00

  • Plasma alpha-synuclein is decreased in subjects with Parkinson's disease.

    abstract::Alpha-synuclein (alphaSN) is implicated in Parkinson's disease (PD) and is the major component of Lewy bodies (LBs). Although alphaSN is mainly expressed in neuronal cells and exists as a cytoplasmic protein, it has been found in body fluids including cerebrospinal fluid and blood. This study explored plasma alphaSN a...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Li QX,Mok SS,Laughton KM,McLean CA,Cappai R,Masters CL,Culvenor JG,Horne MK

    更新日期:2007-04-01 00:00:00

  • Spontaneous neuronal activity in fetuses and newborns.

    abstract::We compared the magnetic cerebral activity of 10 fetal subjects at two different gestational ages. Spontaneous cerebral activity was recorded with a large array magnetometer specially designed to conform to the maternal gravid abdomen during the third trimester of pregnancy. We recorded each fetal subject at least twi...

    journal_title:Experimental neurology

    pub_type: 杂志文章


    authors: Rose DF,Eswaran H

    更新日期:2004-11-01 00:00:00